Genetically confirmed familial hypercholesterolemia in outpatients with hypercholesterolemia  

作　　者：Xu WANG Long JIANG Li-Yuan SUN Yue WU Wen-Hui WEN Xi-Fu WANG Wei LIU Yu-Jie ZHOU Lu-Ya WANG 

机构地区：[1]Emergency & Critical Care Center, Beijing Anzhen Hospital Capital Medical University, Beijing, China [2]Beijing Anzhen Hospital Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, the Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, China [3]Department of Dermatology, Beijing Anzhen Hospital Capital Medical University, Beijing, China [4]Department of Cardiology, Beijing Anzhen Hospital Capital Medical University, Beijing, China

出　　处：《Journal of Geriatric Cardiology》2018年第6期434-440,共7页老年心脏病学杂志（英文版）

基　　金：We greatly appreciate the support of the patients and their families for participation in this study and cardiologists who participated in this study. This work was supported by grants from the National Natural Science Foundation of China （No. 30470722, 30771982 and 30772356） and the Beijing Natural Science Foundation （No. 7032012, 7052021 and No. 7062010）. The authors have no conflicts of interest to declare.

摘　　要：Background Familial hypercholesterolemia （FH） is an autosomal dominant disorder of lipoprotein metabolism which can lead to premature coronary heart disease （pCHD）. There are about 3.8 million potential FH patients in China, whereas the clinical and genetic data of FH are limited. Methods Dutch Lipid Clinic Network （DLCN） criteria was used to diagnose FH in outpatients with hypercholesterolemia. Resequencing chip analysis combined with Sanger sequencing validation were used to identify mutations in the definite FH patients according to DLCN criteria. In silico analysis was conducted in mutations with previously unknown pathogenicity. Then, the novel mutant receptors were transfected into human embryo kidney 293 （HEK-293） cells. The binding and the internalization activities of the mu- tant receptors were analyzed by flow cytometry. Results The prevalence of definite FH in outpatients with hypercholesterolemia in this study is 3.2%. Using genetic testing, one homozygous FH （HoFH）, one heterozygous FH （HeFH） and three compound heterozygous FH patients were confirmed. Eight mutations in low-density lipoprotein receptor （LDLR） gene were identified, in which c.357delG was a novel mutation and co-segregated with the FH phenotype. Bioinformatic analysis confirmed that c.357delG was a pathogenic mutation. Furthermore, when compared with the wild-type LDLRs by flow eytometry analysis, the binding and internalization activities of c.357delG mutant LDLRs were reduced by 35% and 49%, respectively. Conclusions This study identified eight LDLR gene mutations in five patients with definite FH, in which c.357delG is a novel pathogenic mutation. These findings increase our understanding of the genetic spectrum of FH in China.

关 键 词：Familial hypercholesterolemia Low-density lipoprotein receptor MUTATION 

分 类 号：S852.653[农业科学—基础兽医学] TU238.2[农业科学—兽医学]